A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01682863
First received: September 7, 2012
Last updated: February 29, 2016
Last verified: February 2016
  Purpose
This study is to assess the safety and tolerability of two different doses of QVA149 and QAB149 in patients with moderate to severe airflow limitation.

Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: QVA149
Drug: QAB149
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Patients With Adverse Events, Serious Adverse Events, and Death [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
    The overall rate of adverse events reported from initiation through 30 days post last dose.


Secondary Outcome Measures:
  • Time to Premature Discontinuation of Treatment [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
    methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl

  • Change From Baseline in Pre-dose Trough FEV1 [ Time Frame: Day 29, 57,, 85, 141, 197, 253, 309 and 365 ] [ Designated as safety issue: No ]
    Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.

  • Change From Baseline in 1 Hour Post-dose FEV1 Measurements [ Time Frame: Day 1, 29, 57, 85, 141, 197, 253, 309, and 365 ] [ Designated as safety issue: No ]
    Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.

  • Change From Baseline in FVC Measurement at All Post-baseline Time Points [ Time Frame: Day1, 29, 57, 85, 141, 197, 253, 309, and 365 ] [ Designated as safety issue: No ]
    Pulmonary function assessments were performed using centralized spirometry according to international standards.

  • Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)

  • Change From Baseline in Mean Total Daily Symptom Scores [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.

  • Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.


Enrollment: 614
Study Start Date: October 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QVA149 dose 1
QVA149 27.5/12.5 μg capsules
Drug: QVA149
QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
Experimental: QVA149 dose 2
QVA149 27.5/25 μg capsules
Drug: QVA149
QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
Active Comparator: QAB149
QAB149 75 μg capsules
Drug: QAB149
QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI
Drug: Placebo
To mimic QAB149

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female adults aged ≥40 years
  • Patients with stable COPD according to GOLD strategy (GOLD 2011).
  • Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and <80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70.
  • Current or ex-smokers who have a smoking history of at least 10 pack years.
  • Patients with an mMRC ≥ grade 2

Exclusion Criteria:

  • History of long QT syndrome or prolonged QTc
  • Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1.
  • Patients with Type I or uncontrolled Type II diabetes
  • Patients with a history of asthma or have concomitant pulmonary disease
  • Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with persistent atrial fibrillation and controlled with a rate control strategy for at least six months could be eligible
  • Patients who have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of safety
  • Other protocol defined inclusion/exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01682863

  Show 86 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01682863     History of Changes
Other Study ID Numbers: CQVA149A2340  2012-001998-93 
Study First Received: September 7, 2012
Results First Received: June 22, 2015
Last Updated: February 29, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
COPD, QAB149, QVA149, indacaterol maleate, gylcopyrronium bromide

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Glycopyrrolate
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2016